Fluorouracil (5-FU), also known as Adrucil®, is a chemotherapy agent which is in the antimetabolite and pyrimidine analog families of medications that functions by blocking the production of DNA which has the effect of inhibiting cell division thus preventing tumor cells from dividing and growing. 5-FU acts in several ways, but principally as a thymidylate synthase (TS) inhibitor. Interrupting the action of this enzyme blocks synthesis of the pyrimidine thymidine, which is a nucleoside required for DNA replication. Thymidylate synthase methylates deoxyuridine monophosphate (dUMP) to form thymidine monophosphate (dTMP). Administration of 5-FU causes a scarcity in dTMP, so rapidly dividing cancerous cells undergo cell death via due to no thymine. High levels of thymidylate synthase can overcome the effects of 5-FU while high levels of the TYMP protein promotes the activity of 5-FU.
Leucovorin calcium (LV), also known as folinic acid, does not have cancer-fighting properties but is a medication used to decrease the toxic side effects of chemotherapeutic agents. It is most commonly used in combination with 5-fluorouracil to treat colorectal cancer, but it may also be used to treat folate deficiency that results in anemia.
Oxaliplatin, also known as Eloxatin®, is a cancer chemotherapy agent that interferes with DNA replication thus preventing cells from dividing and leading to tumor cell death via apoptosis. Oxaliplatin has been compared with other platinum compounds used for advanced cancers, such as cisplatin and carboplatin. The retention of a bulky DACH ring by activated oxaliplatin is thought to result in the formation of platinum-DNA adducts in tumor cell DNA, which appear to be more effective at blocking DNA replication and are more cytotoxic than adducts formed from cisplatin. The damaged DNA elicits DNA repair mechanisms, which in turn activates apoptosis when repair proves impossible thus killing the tumor cells.
Capecitabine, also known as Xeloda®, is a chemotherapy agent that, once inside the tumor cell, is converted to 5-fluorouracil (5-EU) through which it acts. It belongs to the class of medications known as fluoropyrimidines, which also includes 5-fluorouracil and tegafur. Thus capecitabine, like 5-FU, acts in several ways, but principally as a thymidylate synthase (TS) inhibitor. Interrupting the action of this enzyme blocks synthesis of the pyrimidine thymidine, which is a nucleoside required for DNA replication. Thymidylate synthase methylates deoxyuridine monophosphate (dUMP) to form thymidine monophosphate (dTMP). Administration of capecitabine causes a scarcity in dTMP, so rapidly dividing cancerous cells undergo cell death via due to no thymine. High levels of thymidylate synthase can overcome the effects of capecitabine while high levels of the TYMP protein promotes the activity of capecitabine.
Cisplatin, also known as Platinol®, is a chemotherapy agent that crosslinks DNA in several different ways, interfering with cell division by mitosis. The damaged DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves impossible. Most notable among the changes in DNA induced by cisplatin are the 1,2-intrastrand cross-links with purine bases. These include 1,2-intrastrand d(GpG) adducts which form nearly 90% of the adducts and the less common 1,2-intrastrand d(ApG) adducts. 1,3-intrastrand d(GpXpG) adducts occur but are readily excised by the nucleotide excision repair (NER). Other adducts include inter-strand crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's activity. Interaction with cellular proteins, particularly HMG domain proteins, has also been advanced as a mechanism of interfering with mitosis, although this is probably not its primary method of action. Although cisplatin is frequently designated as an alkylating agent, it has no alkyl group and it therefore cannot carry out alkylating reactions. It is correctly classified as alkylating-like.